Figure 3. Undiseased human I_Kr and I_Ks experiments and model validation.

A) I_Kr. Experimental data are white circles (N = 10 from 7 hearts for steady state activation, N = 7 from 3 hearts for activation and from 2 hearts for deactivation time constants and weights, and N = 10 from 7 hearts for tail currents). Simulation results are lines. From left to right, top to bottom: steady state activation, time constant for activation (fast (solid) and slow (dashed) time constants converge), fast time constant for deactivation, slow time constant for deactivation, relative weight of the fast component for deactivation, and the I–V curve for normalized tail currents. B) Activation/deactivation profiles in response to the voltage steps shown (−40 mV holding potential to +30 mV steps of various duration, followed by a return to −40 mV, top right inset). Experiments are above. Simulations are below. Activation is rapid, occurring within tens of milliseconds. Deactivation is slow, occurring after several seconds. C) Human AP clamp waveform (top), used to elicit 1 µM E-4031 sensitive current (I_Kr, bottom); experiments are on the left, and comparison to simulations using the same AP clamp is on the right. D) I_Ks. Data are from Virág et al.[41] (black circles). Simulation results are solid lines. From left to right: steady state activation, time constant for activation (much slower than deactivation at depolarized potentials), time constant for deactivation (much faster than activation at hyperpolarized potentials), and the I–V curve, showing normalized tail currents.